tbuckley/cabot-search huggingface dataset:
Preliminary outcomes for non-metastatic breast cancer before and during the coronavirus disease 2019 pandemic at community cancer centers.
Authors: Fangzheng Yuan, Ahmed Abdelhakeem, Samantha Blevins, Chelsey Peters, Susan E. Whalen, Ernest Clayton Hymel
Journal: Journal of Clinical Oncology (2022)

e18634 Background: The Coronavirus Disease 2019 (COVID-19) pandemic has changed the delivery of cancer care and may have impacted the treatment outcomes. This study described the preliminary outcomes in non-metastatic breast cancer (BC) patients before and during the COVID-19 pandemic. Methods: This retrospective study included adult patients newly diagnosed with non-metastatic BC at two community cancer centers in southeast Texas. Patients diagnosed from 1/2018-10/2018 were included in the control group. Patients diagnosed from 4/2020-1/2021 were included in the COVID-19 group. The key outcomes were progression free survival (PFS), overall survival (OS), breast conserving surgery (BCS) rate, pathological complete response (PCR) rate, and time to treatment initiation (TTI). Results: The study included 74 patients (Table). The proportion of patients with self-detected BC was numerically higher in the COVID-19 group (55%) compared to the control group (36%), although this was not statistically significant (P = 0.09). The median follow-up periods were 38 (IQR: 36-43) months in the control group and 15 (IQR: 13-17) months in the COVID-19 group. No significant difference was observed in PFS (P = 0.74), with 1-year PFS of 93% (95%CI: 80%-98%) in the control group and 100% in the COVID-19 group. No significant difference was observed in OS (p = 0.22), with 1-year OS of 98% (95%CI 85%-100%) in the control group and 100% in the COVID-19 group. No significant difference was observed in TTI between control (51 days) and COVID-19 groups (52 days) (95%CI: -14 to 13; P = 0.91). Among patients who received neoadjuvant systemic therapy and surgery, BCS rates were 29% (5/17) in the control group and 50% (5/10) in the COVID-19 group (P = 0.42). Among patients who had triple negative or HER2 positive BC and received neoadjuvant systemic therapy and surgery, PCR rates were 57% (4/7) in the control group and 33% (1/3) in the COVID-19 group. Conclusions: Although total patient volume decreased during the COVID-19 pandemic, no significant difference was observed in clinical outcomes when comparing patients diagnosed with non-metastatic BC during and prior to the pandemic. Ongoing monitoring with a larger study population and longer follow-up period will help to elucidate the long-term impact of COVID-19 on BC treatment.[Table: see text]
Relevance of detection of RAF fusion in pan-negative melanoma in routine practice.
Authors: Philippe Jamme, Guillaume Delzenne, Laurent Mortier, Olivier Farchi, Marie Boileau
Journal: Journal of Clinical Oncology (2022)

e21500 Background: Pan-negative melanomas (i.e. without MAPK kinase pathway alteration and C-kit wild type) account for 30% of melanomas (according to the AACR GENIE database). In case of immunotherapy failure, therapeutic options are limited. Oncogene fusions represent a target of interest in many solid cancers (NSCLC, Cholangiocarcinoma, Glioma, GIST, pancreatic acinar carcinoma, thyroid, and prostate cancers). In melanoma, the frequency of oncogene fusion is not well documented and not routinely investigated. Methods: We conducted a single-center retrospective study. The objective was to determine the frequency of oncogene fusion detected by RNA sequencing (Archer Fusion pLex) performed in routine practice, in patients with advanced or metastatic pan negative melanoma. Data on clinical, pathological, and molecular characteristics and patient outcomes were collected. Analysis was carried out on the genetic material available for the diagnosis of the disease except for 1 patient who benefited from a new anatomopathological sample during an unfavorable evolution. In parallel, an extended molecular alteration search was performed using extended targeted NGS (OncoMine Comprehensive Assay panel). Results: We identified 48 patients with an advanced pan negative melanoma between January 2021 and January 2022 with a median age at diagnosis of 63 years. It was a cutaneous melanoma in 72,9 % (35/48) of the cases, a mucous melanoma in 14,5% (7/48) of the cases and a melanoma of unknown primary site in 12,5% (6/48) of the cases. The detection of fusion transcript was made in 89,5 % (43/48) of the cases. We identified 6 patients with a RAF fusion, including 4 BRAF gene fusion (MKLN1-BRAF, AGK-BRAF, SNX29-BRAF, PTPRJ-BRAF) and 2 RAF1 fusion (MAP4-RAF1, EFCC1-RAF1). Of the other molecular alterations, NF1 mutation was the most frequent molecular alteration identified (25 % (12/48) of patients). At lower frequencies, 6,8 % (3/48) of patients had a PI3K mutation, and 8,3 % (4/48) of patients had NOTCH, PTCH1, GNAQ mutations. Among the 6 patients with RAF fusions, all the patients initially received treatment with anti-PD1+/- anti-CTLA4 immunotherapy. After immunotherapy failure, 4 patients benefited from second-line targeted therapy (2 with BRAF and MEK inhibitors combination, 2 MEK inhibitors alone). One patient presented an objective imaging response, the other three patients have not yet benefited from reassessment imaging. Conclusions: In a population of pan negative melanoma, we detected 12,5 % (6/48) of RAF fusion. Fusion detection allowed the introduction of a second line of targeted therapy, in the absence of a validated therapeutic option in 66,6 % (4/6) of cases This study suggests the relevance of detecting RAF fusion in a selected population.
Efficacy and safety of camrelizumab combined with chemotherapy (irinotecan combined with platinum) followed by camrelizumab combined with apatinib in the first-line treatment of advanced small cell lung cancer: A phase II study.
Authors: Jun Ni, Xiaotong Zhang, Ruili Pan, Hanping Wang, Xiaoyan Si, Xiaoxia Cui, Li Zhang
Journal: Journal of Clinical Oncology (2022)

8573 Background: The treatment mode of small cell lung cancer (SCLC) is mainly based on the comprehensive treatment of chemotherapy and radiotherapy. IMpower133 study, suggesting that immune checkpoint inhibitors combined with chemotherapy first-line treatment for advanced SCLC may bring new research directions of clinical benefit. Previous study suggested that the combination of anti-PD-1 antibody camrelizumab and VEGFR-2 inhibitor apatinib significantly improved antitumor effects. The aim of this study was to evaluate the efficacy and safety of camrelizumab combined with chemotherapy (irinotecan combined with platinum) followed by camrelizumab combined with apatinib in the first-line treatment of SCLC. Methods: Extensive-stage small cell lung cancer patients were enrolled in this single-center, single-arm study. During the induction treatment phase, Patients received camrelizumab (200mg q3w), irinotecan (65 mg/m2, q3w) and platinum (cisplatin: 30 mg/m2, carboplatin: AUC=4̃5), after 4-6 cycles, the patient entered the maintenance phase, and then patients received camrelizumab combined with apatinib until disease progression or unacceptable toxicity. Treatment efficacy was assessed every 3 cycles (6 weeks). The primary endpoint is progression-free survival (PFS). Secondary endpoints are objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and overall survival (OS), which are based on RECIST 1.1. Results: At data cut-off (Jan 10, 2022), 20 extensive-stage SCLC patients were enrolled in the study, of which 18 patients were evaluable. Median age was 64 years, male accounts for 85.0% (17/20). Median follow-up was 5.0 months (range 0.4̃17.6 months). Of 18 evaluable patients, no one achieved complete response Partial response was achieved by 17 (94.4%) patients and stable disease exhibited by 1 (5.6%) patient. The ORR and DCR were 94.4% and 100%, respectively. mPFS and mDoR have not been reached. In terms of adverse events (AEs), reactive cutaneous capillary hyperplasia (RCCEP) was observed in 10 (47.6%) patients 10 patients. Grade III-IV AEs were observed in 7 (35.0%) patients with neutropenia, thrombocytopenia, hemoglobin reduction, leukopenia, rash. The rest were grade I-II AEs. Conclusions: The treatment in this study showed impressive ORR and DCR, and acceptable toxicity, and may be a promising method as a first line treatment. Clinical trial information: NCT04453930.
Prediction of significant renal function decline after open, laparoscopic and robotic partial nephrectomy: Refinement of the Martini’s nomogram on the RECORD2 project cohort
Authors: A. Tafuri, A. Mari, R. Tellini, A. Antonelli, E. Brunocilla, U. Capitanio, F. Di Maida, A. Diminutto, P. Gontero, N. Longo, F. Montorsi, F. Porpiglia, A. Porreca, B. Rocco, C. Simeone, R. Schiavina, L. Schips, S. Siracusano, C. Terrone, V. Ficarra, M. Carini, A. Minervini
Journal: European Urology (2022)
Piloting virtual mentorship: Evaluating acceptability and influence on wellness and professional identity in medical oncology (MO).
Authors: Andrea S. Fung, Lorelli Nowell, Arfan R. Afzal, Maclean Harvey Thiessen, Alexi Campbell, Desiree Hao
Journal: Journal of Clinical Oncology (2022)

11022 Background: Despite extensive literature on the value of mentorship in academic medicine, little evidence exists to inform mentorship practices in MO. In 2021, the Canadian Association of Medical Oncologists (CAMO) piloted a national, 6-month virtual mentorship program consisting of 2 group mentoring events and additional 1-on-1 mentoring activities, to better support the needs of MO trainees. Feedback was obtained from participants to gain insight into how virtual mentorship might impact physician wellness and formation of professional identity, and to inform future iterations of CAMO’s virtual mentorship strategy. Methods: All Canadian MO residents/fellows were invited to participate in the program. Electronic surveys were completed by participants at baseline, after each group event, and at program completion. Surveys evaluated the program content and format, and used validated questionnaires for evaluating physician wellness/burnout (Stanford Professional Fulfillment Index [SPFI]), and professional identity (Macleod Clark Professional Identity Scale [MCPIS]). Cohort characteristics and survey responses were summarized using descriptive statistics. Procedures for survey data collection and analysis were ethics approved. Results: At baseline, respondents (n = 38) were predominantly female (63%), and &lt; 35 years (76%). 50% were married. On average, 78% of respondents ranked the virtual group mentoring events as meeting expectations. Program strengths identified by participants included meeting mentors outside of their own centre, meeting other trainees from across the country, and learning more about work-life balance/physician wellness. The main critique was insufficient time for interaction. Of the 34 MCPIS respondents, 94% were pleased to belong to the profession of MO, 91% identified positively with members of their profession and 77% felt like a member of the profession themselves. The average score on the SPFI scale was 2.73±0.71 (n = 34). Although 85% of respondents found their work meaningful, 71% satisfying, and 50% felt they were contributing professionally in valued ways, only 38% met criteria for professional fulfilment (score ≥3.00). 27% met criteria for burnout (score ≥1.33), 15% found their work physically exhausting and 9% found their work emotionally exhausting. Conclusions: CAMO’s pilot virtual mentorship program highlights that technology can be successfully leveraged to facilitate mentoring. The majority of MO trainees identified positively with their profession, yet only 38% reached the threshold for professional fulfillment and nearly a third met criteria for burnout. Longitudinal follow-up among mentored trainees is needed to provide insight into whether mentorship may influence physician wellness and professional identity over time.
Subgroup analysis of patients with no prior chemotherapy in EMERALD: A phase 3 trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), versus investigator’s choice of endocrine monotherapy for ER+/HER2-advanced/metastatic breast cancer (mBC).
Authors: Virginia G. Kaklamani, Aditya Bardia, Philippe Georges Aftimos, Javier Cortes, Janice M. Lu, Patrick Neven, Guillermo Streich, Alberto J. Montero, Frederic Forget, Marie-Ange Mouret-Reynier, Joohyuk Sohn, Donatienne Taylor, Kathleen Kiernan Harnden, Hung T. Khong, Judit Kocsis, Florence Dalenc, Patrick Michael Dillon, Giulia Tonini, Kris Grzegorzewski, François-Clement Bidard
Journal: Journal of Clinical Oncology (2022)

1100 Background: EMERALD demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for elacestrant vs standard of care endocrine therapy (SOC) in patients with ER+/HER2- mBC following progression on prior endocrine and CDK4/6 inhibitor therapy. Benefit was observed in the overall study population and in patients with ESR1 mutations (mESR1). Here, we report a subgroup analysis from EMERALD in patients with no prior chemotherapy. Methods: EMERALD (NCT03778931) is a randomized, open-label, phase 3 trial that enrolled patients with ER+/HER2− mBC who had 1–2 lines of endocrine therapy, mandatory pretreatment with a CDK4/6 inhibitor, and ≤1 chemotherapy. Patients were randomized 1:1 to elacestrant (400 mg orally daily) or SOC (investigator’s choice of fulvestrant or aromatase inhibitor). Primary endpoints were PFS in all patients and patients with mESR1. In this analysis, we compared PFS between elacestrant and SOC in patients without prior chemotherapy. Results: Among the 477 patients enrolled in the trial, 77.8% (n = 371) had not received prior chemotherapy for mBC (median age = 64). Among patients without prior chemotherapy, treatment with elacestrant was associated with significantly prolonged PFS compared to SOC in both the overall population (hazard ratio [HR] = 0.68 [95% CI, 0.52-0.89] P = 0.004; median PFS 3.7 vs 2.0; 6-mo PFS 38% vs 23%; 12-mo PFS 27% vs 12%), and patients with mESR1 (HR = 0.54 [95% CI, 0.36-0.80] P = 0.002; median PFS 5.3 vs 1.9; 6-mo PFS 44% vs 24%; 12-mo PFS 31% vs 12%). Key treatment-related adverse events (AEs) in the no prior chemotherapy elacestrant group were nausea (25.9%), fatigue (12.7%), and hot flush (11.1%). There were no treatment-related deaths in either group. Conclusions: Among patients with ER+/HER2− mBC without prior chemotherapy, elacestrant significantly prolonged PFS compared to SOC endocrine therapy and showed favorable outcomes in this subgroup. Clinical trial information: NCT03778931.
Pyrotinib in combination with metronomic oral vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy: A single-center, single-arm, prospective phase 2 study.
Authors: Chunfang Hao, Xu Wang, Yehui Shi, Zhongsheng Tong, Shufen Li, Xiaodong Liu, Lan Zhang
Journal: Journal of Clinical Oncology (2022)

1033 Background: In 15% to 30% of breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed, this is related to aggressive disease and poor prognosis. Although important clinical benefits for patients have been achieved by the use of the HER2 antibody trastuzumab, 50% to 74% of patients with metastatic disease have no response to treatment, and approximately 75% progress within one year. The purpose of this study was to evaluate the efficacy and safety of oral pyrotinib in combination with oral metronomic vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. Methods: This prospective phase 2 study enrolled patients aged 18-75 years with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy, and had an Eastern Cooperative Oncology Group performance score of 0-2. Patients received pyrotinib 400 mg once daily and vinorelbine 40 mg once on Monday, Wednesday, Friday of each week until disease progression or unacceptable toxicity. Both pyrotinib and vinorelbine were orally administered 30 min after meals. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease remission rate (DCR), overall survival (OS), quality of life (QoL) and safety (CTCAE 5.0). The follow-up of this study is ongoing, but enrolment is closed. This study is registered on Clinical Trials.gov, number NCT04903652. Results: Between Oct 21, 2019, and Jan 21, 2022, 36 patients were enrolled and all of them were included in the intent-to-treat (ITT) population. 20 of 36 patients had disease progress or death. Median follow-up was 16.23 months. The median PFS (mPFS) was 14.23 months (95% CI 8.13-20.33). The ORR and DCR were 38.9% and 83.3%, respectively. The median OS was not reached. Grade 3 adverse events (AEs) occurred in 17 of 36 patients, the most common were diarrhea 27.8% and stomachache 5.6%. No grade 4 AEs were observed. Conclusions: Pyrotinib combined with metronomic oral vinorelbine showed promising efficacy and manageable safety in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. This study might represent a potential treatment option for these patients. Clinical trial information: NCT04903652..
The gain of somatic copy number alteration in both primary and lymph node metastases predict poor prognosis of non-samll cell lung cancer.
Authors: Renping Wan, Zhongying Jing
Journal: Journal of Clinical Oncology (2022)

e20511 Background: Lung cancer is the leading cause of cancer-related mortality among the world, and distant metastases is still the main cause of poor prognosis and cancer-related deaths. Lymph nodes nearby primary tumor is the most commonly metastases. More than 90% NSCLC patients were diagnosed at II or higher stage. Although more and more prognosis molecular biomarkers have been identified, it’s still hard to completely understand the metastases mechanism of NSCLC. Here we work on evaluation whether molecular divergence or common mutational characters in matched primary and lymph node metastases of NSCLC could predict patient’s prognosis. Methods: Within MSKCC(MSK-IMPACT-2017) datasets, 12 matched primary and lymph node metastatic samples were gotten. Molecular divergence and similarity were analyzed between matched samples, including SNVs, fusion mutations, CNA, TMB, signature, concordance between primary and metastatic lymph nodes and relate it to patient’s overall survival. Results: Cox survival analysis results proved that the gain of CNA in both primary and lymph node metastases would be a poor prognosis biomarker for NSCLC. 3/3 NSCLC patients with CNA in both primary and metastases occurred death within 10 months, median OS was 7.76 month. Only 1/9 of the others occurred death at 14 months, other NSCLC patients did not reach the end point of this study. HR for OS with CNA in both matched samples versus the others was 0.07 (95% CI 0.0067-0.67), log-rank p value was 0.0028. Conclusions: The gain of CNA in both primary and lymph node metastases could be a poor prognosis predictor for NSCLC patients.
IMMU-14. SynNotch chimeric antigen receptor (CAR) T-cells as a potential treatment for diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG)
Authors: Lauren Ferrerosa, Milos Simic, Payal Watchmaker, David Diebold, Psalm Pineo-Cavanaugh, Jason Deucker, Wendall Lim, Hideho Okada
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The development of effective chimeric antigen receptor (CAR) T-cell therapies for malignant pediatric brain tumors remains a challenge due to multiple barriers, including antigenic heterogeneity, on-target off-tumor toxicities, and T cell exhaustion. We have adopted a novel synthetic Notch “synNotch” receptor system and developed innovative T-cell circuits that recognize tumor cells based on the “prime-and-kill” strategy. METHODS: We created a novel synNotch-CAR circuit in which the brain/glioma-specific antigen Brevican (BCAN) primes the T cells to induce expression of a CAR that recognizes interleukin-13 receptor α2 (IL-13Rα2) and ephrin type A receptor (EphA2), thereby eradicating glioma cells expressing either antigen. Immunocompromised mice bearing the SF8628 DIPG cell line in the frontal lobe or brain stem received a single intravenous (IV) infusion of synNotch CAR T-cells (2.5 x 106 each of CD4+ and CD8+ T cells) on day 6 following the tumor inoculation. Mice were monitored for toxicity and tumor growth. RESULTS: Following this synNotch CAR T-cell dose, although tumors in the brainstem did not regress, 3 of the 5 mice with frontal lobe tumors demonstrated complete and sustained remission. Our histological analyses revealed primed CAR T-cells both within and surrounding the tumor in both settings. By flow cytometry, we confirmed the CAR T-cells in the CNS were primed and mostly did not express an exhaustive phenotype. In the spleen, we also found the CAR T-cells in a more naïve and central memory state. CONCLUSIONS: Our work so far has demonstrated that synNotch-CAR T-cells are able to traffic to the tumor microenvironment even in the brainstem, are primed to express the CAR, and most do not express an exhaustive phenotype. Future work will include CAR T-cell dose optimization, continued assessments of the tumor microenvironment, and investigating for antigen escape.